Heat shock proteins: protection and potential biomarkers for ischemic injury of cardiomyocytes after surgery

Abstract The heat shock proteins are endogenous proteins with the ability to act as molecular chaperones. Methods that provide cell protection by way of some damage can positively influence the results of surgery. The present review summarizes current knowledge concerning the cardioprotective role of the heat shock proteins as occurs in heart damage, including relevant information about the stresses that regulate the expression of these proteins and their potential role as biomarkers of heart disease.

Energy-responsive timekeeping.

An essential component of energy homeostasis lies in an organism's ability to coordinate daily patterns in activity, feeding, energy utilization and energy storage across the daily 24-h cycle. Most tissues of the body contain the molecular clock machinery required for circadian oscillation and rhythmic gene expression. Under normal circumstances, behavioural and physiological rhythms are orchestrated and synchronized by the suprachiasmatic nucleus (SCN) of the hypothalamus, considered to be the master circadian clock. However, metabolic processes are easily decoupled from the primarily light-driven SCN when food intake is desynchronized from normal diurnal patterns of activity. This dissociation from SCN based timing demonstrates that the circadian system is responsive to changes in energy supply and metabolic status. There has long been evidence for the existence of an anatomically distinct and autonomous food-entrainable oscillator (FEO) that can govern behavioural rhythms, when feeding becomes the dominant entraining stimulus. But now rapidly growing evidence suggests that core circadian clock genes are involved in reciprocal transcriptional feedback with genetic regulators of metabolism, and are directly responsive to cellular energy supply. This close interaction is likely to be critical for normal circadian regulation of metabolism, and may also underlie the disruption of proper metabolic rhythms observed in metabolic disorders, such as obesity and type-II diabetes.

Exercício e proteínas de estresse(Hsp 72) no músculo cardíaco / Exercise and stress proteins (Hsp 72) in cardiac muscle

As proteínas de estresse foram inicialmente denominadas como proteínas de choque térmico (Heat Shock Protein - HSP), pois a expressão destas proteínas estava aumentada em células de Drosófilas após serem submetidas a um tratamento térmico. Atualmente, sabe-se que células de todos os seres vivos possuem essas proteínas e que várias outras formas de estresse induzem sua expressão. A família HSP 70 é a mais estudada e, dentre as isoformas, apenas a Hsp 72 é exclusivamente induzida. Tais proteínas exercem um papel de proteção ao organismo contra episódios de estresse. A indução da expressão das Hsp 72 é promovida pelo exercício físico e parâmetros como volume, intensidade e modelo de exercício podem afetar sua expressão. Porém, deve-se considerar que eventos fisiológicos e metabólicos, tais como, aumento da temperatura corporal, alteração dos níveis de catecolaminas, cálcio, glicogênio, ATP, lactato e das espécies reativas de oxigênio, ocorrem nas células durante o exercício, os quais podem modular a expressão de Hsp 72, o que a coloca como um fenômeno multifatorial. Estudos mostram que os benefícios promovidos pelo exercício como proteção, prevenção e recuperação do miocárdio após infarto ou eventos de isquemia, estão condicionados ao aumento das Hsp 72. O aumento da expressão das Hsp 72 pelo exercício coloca-se, então, como uma explicação, pelo menos parcial, da proteção cardíaca promovida pela prática regular de atividade física.

Stress proteins were first named as Heat Shock Protein (HSP) once its expression was increased in drosophila cells after heat shock. At the moment it is known that such proteins are present in all live organisms and that many types of stress induce its expression. HSP 70 family is the most studied and only Hsp 72 is induced. Stress proteins have a role in the protection of live organisms against stress events. Hsp 72 expression is induced by physical exercise and volume, intensity and the model of exercise may affect its expression. Nonetheless, it has to be kept in mind that physiological and metabolic events such as increase in body temperature, alteration in the levels of catecholamines, calcium, glycogen, ATP, lactate and reactive oxygen species occurs during exercise which may modulate Hsp72 expression and so its expression may be recognized as a multifactorial phenomenon. Studies show that the beneficial effects of exercising such as cardiac protection and recovering of the myocardium after infarction or ischemia events are associated to increases in Hsp72 levels. The increased expression of Hsp72 in response to exercise may therefore explain at least partially the cardiac protection promoted by physical activity.

Biologia de las proteinas del shock térmico / Biology of heat shock proteins

Las proteínal del shock térmico (Hsp) constituyen una família que se encuentra en forma constitutiva en todas las células pro y eucariotas. Cumplen diversas funciones fisiológicas: colaboran en la adquisición de la estructura terciarua de las proteínas en formación, interviniendo en su ensamble, translocación y secreción así como también en la degradación o reparación de proteínas anormales, actuando como chaperonas moleculares. Cuando las células son sometidas a distintos estímulos como el estrés del shock calórico, radiaciones, diversas drogas, infecciones virales, etc, las Hsp se sobreexpresan. De esta manera confieren protección a las células, volviéndolas resistentes a la apoptosis. Esta familia de proteínas comprende numerosos miembros que se agrupan según su peso molecular. En los seres humanos, las Hsp se expresan también en tejidos neoplásicos de ovario, endometrio, mama, aparato digestivo, etc. En algunos casos, la sobreexpresión está asociada a mal pronóstico de la enfermedad debido a que podría favorecer el proceso metastásico. Algunos autores las correlacionan tanto con la proliferación como con la diferenciación de los tejidos neoplásicos. Recientes estudios muestran su influencia en el desarrollo de la resistencia a drogas quimioterapéuticas. En enfermedades autoimunes, como artritis reumatoidea, las Hsp pueden suprimir la respuesta inflamatoria. En otras enfermedades pueden resultar inmunógenas por sí mismas. Por consiguiente su papel en el sistema inmune aún no está bien definido.

Avances en el conocimiento de las proteínas de estrés (HSP) en reumatología / Advances in the knowledge of the heat-shock proteins in rheumatology

Las proteÝnas de estrÚs, o tambiÚn llamadas de shock tÚrmico (hsp), estßn constituidas por un grupo de proteÝnas que son sintetizadas por las cÚlulas contra diferentes estÝmulos, entre los cuales se cuenta el calor. La función de estas hsp pareciera estar estrechamente relacionada con los mecanismos protectores que tiene la cÚlula frente a distintos agentes agresores. De los mecanismos descritos, el relacionado con la neutralización de los productos oxidativos pareciera ser uno de los mßs relevantes. Desde el punto de vista clÝnico, las hsp han adquirido relevancia debido a que poseen una elevada inmunogenicidad y porque presentan un alto grado de homologÝa con agentes bacterianos, entre los cuales se cuentan las micobacterias. Esta similitud antigÚnica entre hsp exógenas (bacterias) y algunas propias de nuestro organismo, podrÝa dar origen a respuestas autoinmunes, como se aprecia en las artritis reactivas o artritis reumatoidea (AR). Estudios efectuados con diversas tÚcnicas de laboratorio con el fin de medir anticuerpos contra la hsp de Micobacterium tuberculosis o bovis (hsp 65 kDa) en pacientes con AR, han dado cifras elevadas en comparación a los controles. En paÝses donde existe una incidencia mayor de TBC, como ocurre con algunas zonas de Africa, esta diferencia es menor. La respuesta mediada por linfocitos T en enfermos portadores de AR, especialmente los procedentes de lÝquido sinovial, exhibe tambiÚn una gran reactividad a la hsp 65 kDa de micobßcterio. El conocimiento de las hsp constituye un nuevo mecanismo patogÚnico que podrÝa relacionar a los agentes microbianos y ciertas fonnas de artritis, especialmente AR y algunas variedades de artritis reactivas

New vaccines against tuberculosis

It has proved difficult to vaccinate effectively against tuberculosis with mycobacterial components or even with whole dead mycobacteria;protection was always inferior to that obtained with the live attenuated vaccine known as bacillus Calmette-Guérin (BCG). We have found that this may no longer be the case. Expression of the gene for a single mycobacterial antigen (Mycobacterium leprae hsp 65) in adult BALB/c mice resulted in substantial cell-mediated protection agains challenge with M. tuberculosis, but only when it was generated as an endogenous antigen within antigen-presenting cells. CD4 and CD8 T cells cloned from spleens of immunized mice passively transferred protection to non-immunized mice, and CD8 cells selectively lysed macrophages infected with M. tuberculosis. The ability of the clones to protect recipient mice against challenge infection was most strongly associated with specific cytotoxic capacity and secondarily with IFN-gamma production. Three modes of expressing the gene have been tested: a)expression froma retroviral vector (pZIPNeoSV) in implanted J774 tumor cells, b)expression from the same vector via bone marrow cells transfected in vitro and used to reconstitute irradiated mice, and c)in a preliminary experiment, from cytomegalovirus (CMV) immediate-early and hydroxymethylglutaryl Co-A reductase promotors injected as plasmid DNA into muscle.

Efecto de polimixina B sobre el mecanismo hemolítico del género Listeria / Effect of polymyxin B on the hemolytic mechanism of the genus Listeria

El contacto de polimixina B, sobre hematíes humanos produjo un efecto sobre la actividad hemolítica de las hemolisinas del género Listeria. A bajas concentraciones de antibiótico, se observó un efecto promotor de la hemólisis; verificándose una inhibición de la lisis eritrocitaria a altas concentraciones de polimixina B. Este comportamiento permitió definir perfiles hemolíticos para cada una de las especies hemolíticas del género en estudio. Listeria monocytogenes y Listeria seeligeri presentaron perfiles superponibles con un máximo hemolítico a 1.000 U/ml de polimixina B. Listeria ivanovii presentó dos picos hemolíticos: uno coincidente con aquél presentado por Listeria monocytogenes y Listeria seeligeri a 1.000 U/ml y un segundo pico a 4.000 U/ml de polimixina B

Activation of yeast trehalase by heat shock

1. Activation of Saccharomyces cerevisiae trehalase by heat shock was shown in all strains tested, including mutants in which the reponse to a glucose signal was absent. A low concentration of cAMP favored the response as seen in 2nd log cells or in ras2 and cyr1ts mutant strains. The heat shock effect upon trehalse activity was not observed under conditions of catabolite repession. 2 Neither hexokinase PII nor the heat shock protein hsp26 seemed to be involve in the axtivation of trehalase by heat shock. However, mutant strains deleted in the polyubiquitin gene showed only a 2-fold activation of the enzyme while in control strains a 5-to 7-fold irreversible activation was observed. 3. An alternative mechanism of trehalase activation by removal of an inhibitor through ligation with ubiquitin is discussed. Activation by cAMP-independent phosphorylation is also considered